Table 1 Detailed inclusion and exclusion criteria

Inclusion criteria

o Age 40–85 years

o Short Portable Mental Status Questionnaire (SPMSQ) also named Pfeiffertest ≥7

o Male and females

o The primary THA performed between 7 to 20 years before inclusion.

o The primary THA performed due to osteoarthritis or congenital dysplasia of the hip.

o Uncemented cup fixation

o Baseline osteolytic lesion of at least 4 cm³ and at most 40 cm³ around an uncemented acetabular component with a polyethylene liner.

o Participant is willing and able to follow study protocol and has provided informed consent prior to any study specific procedures.

Exclusion criteria

o For women of childbearing potential: Subject refuses to use 1 highly effective method of contraception (contraceptive pill, intra uterine contraceptive device) for the duration of the study and for 10 months after the last dose of study medication.

o For males with a partner of childbearing potential: Subject refuses to use 1 highly effective method of contraception for the duration of the study and for 10 months after the last dose of study medication.

o For males with a partner who is pregnant: Subject refuses to use a condom for the duration of the study and for 10 months after the last dose of study medication.

o Pain in the operated hip (because the presence of hip pain in combination with an osteolytic lesion is an indication for revision surgery). VAS > 3

o Previous revision surgery of the hip i.e. exchange of any inplant after the primary surgery

o Inflammatory arthritis

o Previous participation in clinical trials with Denosumab or administration of commercial Denosumab (Prolia™ or Xgeva™)

o Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s).

o Treatment with any intravenous bisphosphonate, fluoride (except for dental treatment) or strontium ranelate within 5 years prior to inclusion.

o Treatment with any oral bisphosphonate within 1 year prior to inclusion.

o Treatment with cortisol or cytostatic drugs within 6 months prior to inclusion.

o Administration of any of the following treatments 3 months prior to screening:

 • Anabolic steroids or testosterone

 • Glucocorticosteroids (≥ 5 mg prednisone equivalent per day for more than 10 days or a total cumulative dose of ≥ 50 mg)

  • Calcitonin

 • Calcitriol or vitamin D derivatives [vitamin D contained in supplements or multivitamins is allowed]

 • Other bone active drugs including anti-convulsives (except benzodiazepines) and heparin

 • Chronic systemic ketoconazole, ACTH (adrenocorticotrophic hormone), cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists.

 • Androgen deprivation therapy

o Hypocalcaemia.

o Bone metabolic disorders (such as OI, PHPT, Paget)

o History of osteonecrosis of the jaw and/or recent tooth extraction or dental surgery; or planned invasive dental proceedures during the study

o Serum 25-OH D < 20 ng/ml

o Significant malabsorption including Celiac Disease, Short Bowel Syndrome, Crohn’s Disease, Previous Gastric Bypass.

o Active cancer and/or malignancy in last 5 years (except cervical carcinoma in situ or basal cell carcinoma)

o History of solid organ or bone marrow transplant.

o Hypersensitivity to any components of study drug.

o Intolerance to calcium supplements.

o Pregnancy and/or currently lactating.

o Significantly impaired renal function as determined by a derived glomerular filtration rate (GFR) using Cockcroft Gault formula of ≤ 30 mL/min/1.73 m2

o Elevated transaminases ≥ 2.0 x upper limit of normal (ULN); Elevated total bilirubin (TBL) > 1.5 x ULN.